A major obstacle to the widespread medical use of THC, the key mind-altering ingredient of marijuana, will begin to fall in the next few weeks as the Drug Enforcement Administration begins the process of taking THC off of a list prohibiting its general use for any purpose.
Although it has been available for experimental purposes under a special exemption of the Controlled Substances Act, THC, along with marijuana, has up to now been on Schedule 1, a list of drugs with no known medical use but significant potential for abuse.
"We are considering rescheduling it to Schedule 2, the highest schedule of control for drugs which have a legitimate medical use such as morphine and cocaine , but which also have a high potential for abuse," says Gene R. Haislip, DEA's deputy assistant administrator for diversion control.
The rescheduling proposal is "soon to be published in the Federal Register," Haislip says. "I am hoping it will be within not more than several weeks." A period for public comment would follow publication in the register, so it may take months before a final decision is made.
If THC is rescheduled, Unimed Inc., a small New Jersey drug company that sells no other products in the American market, will become the sole U.S. supplier of legal delta-9-tetrahydro-cannabiol, the full name for THC. Unimed, the only drug company so far to publicly show any interest in selling this natural substance which cannot be patented, will market the drug as Marinol.
DEA decided to pursue rescheduling THC because the Food and Drug Administration concluded earlier this summer that THC is both safe and effective in controlling the severe nausea and vomiting caused by the poisonous drugs used to kill cancer cells. The FDA decision gave Unimed the approval it needed to begin selling Marinol, but the restrictive listing stopped the company from putting it on the market.
Even as it nears the marketplace, however, the wave of enthusiasm that turned THC into a glamor drug at the end of the 1970s seems to be fading. Although several studies have confirmed that THC does control nausea and vomiting in more than half of the patients receiving cancer chemotherapy, it has not proved to be the panacea some scientists thought. Newer drugs, released since 1980, have been shown to be as effective or more effective in controlling nausea and vomiting without the mood-altering side effects of THC.
And claims that THC can be used to treat everything from glaucoma to epilepsy to multiple sclerosis have either not been substantiated or researchers have lost interest because of technical difficulties with the THC preparations.
"I can't give it a ringing endorsement," says Dr. Richard J. Gralla, a cancer expert at Memorial Sloan-Kettering Cancer Center in New York and a THC researcher for the last eight years. "Most studies show it to be equivalent to Compazine or slightly better. Overall, there are a variety of antiemetics drugs that control vomiting which are much more potent than THC.
"Most physicians feel that they can get along without THC," Gralla says. "If it were not a marijuana derivative, you would not be writing this story." "We have not been using it very much here," says Dr. Robert S. Siegel, an oncologist at George Washington University Medical Center, where THC is available to patients in an experimental program. "The difference between now and five years ago is that we have these additional drugs, making the availability of THC something that is less than critical."
Even Unimed's package insert warns that: "Marinol is indicated for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. This restriction is required because a substantial proportion of patients treated with Marinol can be expected to experience disturbing psychotomimetic reactions or symptoms which mimic a psychosis not observed with other antiemetic agents."
THC's "toxicity" is the problem. The THC pill will make patients "high" just as if they had smoked a marijuana cigarette.
To a young person who has used the street drug, this high may not be a problem, and may even be enjoyable. For older patients, however -- and most cancer patients are older than 60 -- the mood-altering side effects of THC can be frightening.
"It can be pretty upsetting to have cancer and be getting chemotherapy for the first time," says Memorial Sloan-Kettering's Gralla. "You are in a hospital room and you are a little frightened and then they give you a mood-altering drug. That can be a little disconcerting."
"In some studies, the side effects of THC for some patients have been devastating," says Dr. Charles Moertel, director of the Mayo Clinic's cancer center. "Some of the elderly patients have been thrown into sufficient side effects that they required hospitalization for psychiatric care."
Other side effects include sedation, dizziness, hallucinations, disorientation and, in some patients, disphoria -- altered or bad moods.
Besides treating the side effects of chemotherapy, THC has been touted as a possible treatment for a variety of disorders, including glaucoma, epilepsy and even multiple sclerosis. None of these claims, however, have led to new treatments for these diseases, and there appears to be very little research currently under way.
"We have nobody working in epilepsy with THC," says Edward Tocus, chief of the FDA's drug abuse staff, which oversees all research with THC. "We have nobody working in multiple sclerosis either. I do have a couple of physicians with individual [multiple sclerosis] patients, and that is as far as it goes."
"We have been doing some work on glaucoma," says Dr. Coy W. Waller of the Research Institute of Pharmaceutical Sciences at the University of Mississippi in Oxford. "There is no question that [THC] will lower intraocular [eye] pressure."
THC appears to be effective in open-angle glaucoma, the most common form of this disorder, in which the internal pressure of the eyeball rises uncontrollably and destroys the optic nerve, causing blindness.
The problem, however, Waller says, is getting the THC to the eye. Glaucoma patients first tried smoking marijuana and then tried THC capsules. "Then we tried to work out drops," says Waller, a pharmacologist. "That is where we ran into trouble. THC is about like axle grease; it is very thick. You can get it to dissolve for preparations only in those things that are extremely irritating, such as gasoline. The drops that have been prepared have not given good effects in humans and are irritating."
"The vast majority of ophthalmologists are not looking for this as a significant addition. It just has not done it," says Dr. Bruce Spivey, executive vice president of the American Academy of Ophthalmologists in San Francisco. "It has been tested, it has been tried. It has not been found to in any way to be a replacement or a significant addition to what we have now. There are far better medications."
"Ophthalmologists are generally not interested, even if it works," FDA's Tocus says. "We have essentially no applications from ophthalmologists who even want to study it," and no company, including Unimed, has proposed marketing THC to treat glaucoma.
Besides the loss of enthusiasm among doctors, the approval of THC may get hung up on one other technicality: its rescheduling may violate international treaties for controlling drug abuse.
"The international treaty that this drug is under is called the Convention on Psychotropic Substances of 1971, signed by about 76 countries including the U.S.," says DEA's Haislip. "The treaty is similar to the law of the U.S. in that it sets up schedules of control for various drugs."
THC is listed on a schedule that "prohibits all uses except for scientific and very limited medical purposes."
In anticipation of rescheduling THC in the United States, the government asked the World Health Organization, which decides how a drug is scheduled under the treaty, to move THC off of the most restrictive list. WHO rejected that proposal.
"This is an issue which is a primary factor in formulating our decision, which we are now doing," says Haislip. He refused to spell out exactly how the administration planned to reschedule THC without violating the treaty requirements.
Even if THC is rescheduled, it will not be immediately available in all states. Each state have its own controlled substances lists, which may not immediately change just because the federal government reschedules a drug.
And even if all of the legal problems are solved, there are medical experts who think it will not have been worth the hassle.
"For the more really troublesome problems of nausea and vomiting, we now have better ways of handling that without using THC," says the Mayo Clinic's Moertel. "I seriously question whether THC has any important role in the management of cancer patients today."